The goal of this proposed midcareer investigator award is to expand training in multi- disciplinary research focused on the environmental health sciences at the University of Washington. Through collaborations with several ongoing training programs, the candidate, Joel D. Kaufman, MD, MPH, will extend a broad research program and mentoring program with trainees from several relevant disciplines. During the initial K24 award period, Dr. Kaufman's research productivity and mentorship increased and accelerated in depth and breadth. This continuing program will integrate experimental, epidemiologic, and translational approaches to the role of environmental factors in cardiovascular disease. The proposed research is a combination of two thematically related projects from Dr. Kaufman's ongoing research program. Both address the thesis that traffic-related air pollution exerts an effect on cardiovascular diseases through acute and chronic impacts on the vascular system. One project studies the effect of diesel exhaust inhalation on vascular function in controlled exposures, addressing mechanistic hypotheses to understand the role of oxidative stress. The second project is based in an epidemiological study of air pollution effects on cardiovascular disease, and examines the joint and independent effects of acute and chronic pollution exposures on vascular function, atherosclerosis, and epigenomic markers, in a multi-ethnic population-based cohort. The mentorship program builds on Dr. Kaufman's success in multi-disciplinary research, and aims to provide research mentorship in patient-oriented environmental health sciences research to trainees from a wide variety of disciplines. These will include fellows in occupational and environmental medicine, cardiology, and pulmonary medicine; medical students; and graduate students in epidemiology, toxicology, occupational and environmental hygiene, biostatistics, and environmental engineering. The program will include a research infrastructure (research assistance, data analysis, and biostatistics) and supervised research mentorship. The University of Washington provides an outstanding setting for collaborative training and patient-oriented research in environmental health sciences.